Human immunodeficiency virus (HIV-1) is the major cause of acquired immunodeficiency syndrome (AIDS) in humans. A prophylactic vaccine is urgently needed to curb the HIV-1 pandemic. The elicitation of virus-neutralizing antibodies by an HIV-1 vaccine would be desirable. The HIV-1 envelope glycoproteins, gp120 and gp41, are the only targets on the virion accessible to neutralizing antibodies. The HIV-1 envelope glycoproteins are contained in trimeric complexes on the viral surface, and mediate receptor binding and membrane fusion. Strategies for eliciting broadly effective neutralizing antibodies have yet to be devised, at least in part because the available immunogens imperfectly mimic the functional envelope glycoprotein complex. We have created solid-phase proteoliposomes containing trimeric HIV-1 envelope glycoproteins anchored in a lipid membrane. The specific aims of this proposal are: 1) To create proteoliposomes containing envelope glycoproteins that effectively mimic the functional HIV-1 envelope complex; 2) To use the Env-proteoliposomes to select novel oligomer-specific ligands from phage-display libraries; and 3) To evaluate the immunogenicity of Env-proteoliposomes.